BRS Biochem - Carb Metab

Question 1

defects in the enzyme of the hexose monophosphate shunt result in hemolytic anemia on exposure to oxidative agents

Answer 1

Glucose-6-phosphate dehydrogenase (G6PDH)
(the hexose monophosphate shunt pathway generates NADPH-reducing equivalents, necessary to regenerate glutathione, which protects against oxidative damage to hemoglobin)

Question 2

a condition due to deficiency of alpha-L-iduronidase, a lysosomal enzyme, with the accumulation of the glycosaminoglycans heparan sulfate and dermatan sulfate

Answer 2

Hurler syndrome
(accumulation of glycosaminoglycans in the heart, brain, liver, and other organs results in hepatomegaly, dwarfism, gargoyle-like facies, corneal clouding, mental retardation, and death by age 10.)

Question 3

a condition due to X-linked deficiency of the lysosomal enzyme L-iduronosulfate sulfatase, with accumulation of heparan sulfate and dermatan sulfate

Answer 3

Hunter syndrome
(results in hepatomegaly, mild mental retardation, and no cataracts; demonstrates less severe symptomatology than Hurler syndrome.)

Question 4

a benign condition due to a genetic deficiency of fructokinase, which may be found incidentally due to an elevated “glucose” concentration in the urine on dipstick testing.

Answer 4

Essential fructosuria
(results in the accumulation of fructose in blood and urine, which, like glucose, is a reducing sugar that will give a falsely elevated "glucose" concentration on dipstick screening)

Question 5

deficiency of this glycolytic enzyme leads to the second most common enzyme-deficiency hemolytic anemia

Answer 5

Pyruvate kinase
(deficiency results in inadequate production of ATP, which is needed by sodium channels to maintain osmotic equilibrium; the result is membrane lysis.)

Question 6

rarely congenital, this acquired disaccharidase deficiency results in gas, bloating, and watery diarrhea upon consumption of dairy products

Answer 6

Lactase deficiency
(inability to break down lactose into glucose and galactose leads to osmotic diarrhea as well as increased fermentation by intestinal flora.)

Question 7

this disorder results from a genetic deficiency of galactose-1-phosphate uridyltransferase, with accumulation of galactose-1-phosphate in tissues

Answer 7

Classic galactosemia
(results in failure to thrive, infantile cataracts, mental retardation, and cirrhosis, with liver failure and death; can be prevented by excluding galactose from diet early in life (no breast milk -> lactose))

Question 8

this disorder represents the less severe albeit less common form of galactosemia

Answer 8

Galactokinase-deficient galactosemia

a defect in the first enzyme in the catabolism of galactose results in infantile cataracts

Question 9

this lysosomal storage disease results from a deficiency in the enzyme that adds a mannose-6-phosphate moiety, which is required to target proteins to the lysosome

Answer 9

I-cell disease
(proteins destined to be targeted through the endoplasmic reticulum require the presence of a mannose-6-phosphate tag, they are released via the default secretory pathway to the outside of the cell. Release of such hydrolytic enzymes results in the buildup of partially degraded materials in intracellular inclusions)

Question 10

this disorder results from a genetic deficiency of muscle phosphorylase, with accumulation of glycogen in skeletal muscles

Answer 10

McArdle disease
(following exercise, results in painful muscle cramps and weakness due to rhabdomyolysis. Patients may experience bouts of myoglobinuria, which can lead to renal failure)

Question 11

this disorder results from a deficiency of the glycogen debranching enzyme amylo-1,6-glucosidase

Answer 11

Cori disease
(this leads to the accumulation of glycogen in the liver, heart, and skeletal muscle which becomes manifest as stunted growth, hepatomegaly, and hypoglycemia)

Question 12

this disorder results from a defect in the lysosomal enzyme alpha-1,4-glucosidase, leading to the accumulation of glycogen within the organelle

Answer 12

Pompe disease
(results in the accumulation of glycogen in the liver, heart, and skeletal muscle; death by age 3 is usually due to cardiomegaly and heart failure)

Question 13

this disorder results from the AR deficiency of glucose-6-phosphatase

Answer 13

Von Gierke disease
(results in the accumulation of glycogen in the liver and kidney and presents with hepatomegaly and hypoglycemia. This is the most common glycogen storage disease)

Question 14

can result from the AD deficiency of the glycolytic enzyme glucokinase; results in severe beta-cell defects in insulin secretion

Answer 14

Maturity-onset diabetes of the young (MODY)
(other AD deficiencies resulting in MODY include mutations in hepatocyte nuclear transcription factor (HNF)-1alpha and HNF-4alpha)

Question 15

this genetic deficiency of a glycolytic enzyme leads to the accumulation of fructose-1-phosphate and inhibition of glucose production

Answer 15

Aldolase deficiency
(deficiency results in fructose intolerance and life-threatening hypoglycemia upon fructose consumption)

Question 16

this mucopolysaccharidosis is due to a deficiency of beta-glucuronidase, with accumulation of heparan sulfate, dermatan sulfate, and chondroitin 4,6 sulfate

Answer 16

Sly syndrome
(patients present with hepatomegaly, skeletal muscle deformity, and developmental delay. AR lysosomal storage disease. Although experimental, much work has been accomplished in preparing the way for treatment of this disorder with gene therapy)

Question 17

this form of mucopolysaccharidosis results from accumulation of heparan sulfate secondary to a genetic deficiency of heparan sulfamidase, N-acetylglucosaminidase, or N-acetylglucosamine 6-sulfatase

Answer 17

Sanfilippo syndrome
(all three forms of Sanfilippo syndrome (A, B, and C), result from the corresponding enzyme deficiencies; they result in the developmental delay, loss of motor skills, and death by the second decade of life. rare AR lysosomal storage disease)

Question 18

this disorder results from a genetic deficiency of galactose-6-sulfatase, leading to the accumulation of keratin sulfate and chondroitin 6-sulfate

Answer 18

Morquio syndrome
(unlike other mucopolysaccharidoses, Morquio syndrome is not associated with CNS involvement. The main features of the disease are severe skeletal dysplasia and short stature. Motor involvement results from spinal cord impingement on motor neurons)

Question 19

this glucose transporter is the primary transporter in hepatocytes. It is insulin-independent and allows the liver to respond appropriately to serum glucose concentrations

Answer 19

GLUT-2
(genetic deficiency of this important hepatic transporter results in a type XI glycogen storage disease. Patients present much like those with von Gierke’s disease, with hypoglycemia, ketonuria, and hypercholesterolemia)

Question 20

This diabetic medication works by inibiting hepatic gluconeogenesis, thereby decreasing serum glucose levels

Answer 20

Metformin
(patients with type II diabetes have significantly increased rates of gluconeogenesis. Metformin, a member of the biguanide class of agents, is important in the treatment of type II diabetes, particularly in those with coexisting obesity)

Question 21

this class of agents, used in the treatment of type II diabetes, induces genes that increase the cell’s responsiveness to circulating insulin

Answer 21

Thiazolidinediones
(diabetes is typically diagnosed when patients have fasting blood sugars above 126 mg/dL on two separate occasions. Alternatively, patients with blood glucose > 200 mg/dL on the oral glucose tolerance test after 2 hours are diagnosed with diabetes)

Question 22

this metabolite results from the conversion of the aldehyde group of glucose to an alcohol by the action of the enzyme aldose reductase

Answer 22

Sorbitol
(this metabolite accumulates in cells, increasing the osmotic pressure and promoting cell swelling. Ultimately, damage occurs, resulting in injury to nerves and the lens of the eye and accounting for some of the long-term complications of type II diabetes)

Question 23

this blood group antigen results from the addition of N-acetylgalactosamine to the H substance of antigens on red blood cells

Answer 23

A blood group antigen
(the addition of this moiety by N-acetylgalactosamie transferase occurs on the nonreducing end of the H antigen, a fructose-linked to a galactose residue.)

Question 24

this blood group results from the transfer of galactose to the nonreducing end of the H substance found on the surface proteins of red blood cells

Answer 24

B blood group
(patients with the AB blood group possess both and N-acetylgalactosamine transferase (formation of an A antigen) and a galactosyl transferase (formation of the B blood group antigen). Patients with the O blood group do not have either transferase and produce no additional modifications to the H antigen)

Question 25

This molecule is composed of a core protein with repeating disaccharides of uronic acid and glucosamine

Answer 25

Heparin
(this therapeutically important glucosaminoglycan is used as an anticoagulant in the management of myocardial infarction and in the prevention of deep venous thrombosis)

Question 26

this enzyme, activated by the Ca++ efflux from the sarcoplasmic reticulum during muscle contraction, activates glycogen phosphorylase, thus liberating glucose monomers for use in glycolysis

Answer 26

Phosphorylase Kinase
(the genetic deficiency of this enzyme causes a type IX glycogen storage disease. The most common form is X-linked, resulting in hepatomegaly, growth retardation, and delayed motor development)

Question 27

this disorder results from a partial genetic deficiency of the liver isozyme that normally liberates glucose monomers from the nonreducing ends of glycogen

Answer 27

Hers disease
(complete deficiency of glycogen phosphorylase, the enzyme that liberates glucose-1-phosphate from glycogen to maintain blood glucose during fasting, would be lethal. Instead, patients have a partial deficiency with mild hypoglycemia and, rarely, liver enlargement)

Question 28

this disorder results from a deficiency of a glucosyl 4:6 transferase that is important in forming the branches during glycogen synthesis

Answer 28

Andersen disease
(this type IV glycogen storage disease results in glycogen with very long outer branches. Patients develop cirrhosis of the liver, with death occurring in early childhood.)

Question 29

This key regulatory enzyme in the formation of glycogen transfers glucose residues from UDP-glucose to the nonreducing ends of a glycogen primer

Answer 29

Glycogen synthase
(the genetic deficiency of this enzyme results in a type 0 glycogen storage disease that manifests with fasting hypoglycemia and muscle cramping)

Question 30

this important allosterically regulated enzyme of the glycolytic pathway represents the first committed step in glycolysis

Answer 30

Phosphofructokinase I (PFK1)
(this enzyme is activated by fructose-2,6-bisphosphonate and AMP and is inhibited by ATP and citrate. Genetic deficiency of this enzyme results in a type VII glycogen storage disease causing hemolytic anemia and muscle cramping)

Question 31

formed as a side product of 1,3-bisphosphoglycerate in red blood cells, this intermediate is capable of altering hemoglobin’s affinity for oxygen

Answer 31

2,3 Bisphosphoglycerate (BPG)
(BPG decreases the affinity of hemoglobin for oxygen, thus facilitating oxygen release in tissues. Fetal hemoglobin has a lower affinity for BPG and therefore a higher affinity for oxygen, facilitating the transfer of oxygen from mother to fetus at the placental interface)

Question 32

This glycolytic enzyme converts 2-phosphoglycerate to phosphoenolpyruvate (PEP), which contains a high energy enol phosphate

Answer 32

Enolase
(this enzyme in inhibited by fluoride, which is used in samples collected for sensitive glucose tolerance testing, to prevent ongoing glycolysis)

Question 33

this glycolytic enzyme isomerases the carbon sugar dihydroxyacetone phosphate to glyceraldehyde 3-phosphate

Answer 33

Triose phosphate isomerase
(although rare, a genetic deficiency of this enzyme results in neonatal onset hemolytic anemia, progressive neurological impairment, and cardiomyopathy)

Question 34

this protein cotransports sodium and glucose into the cell in an insulin-independent manner and is widely expressed on cells, although most abundantly on red blood cells

Answer 34

GLUT-1
(as red blood cells lack mitochondria, they are completely reliant on glycolysis and are therefore insulin-independent. Hereditary deficiency of GLUT-1 has been reported, with decreased glucose in the CSF, predisposing to the development of seizures)

Question 35

this pharmacologic agent inhibits the enzyme alpha-amylase and alpha-glucosidase, the enzymes that normally cleave the alpha-1,4 and alpha-1,6 linkages between dietary carbohydrates

Answer 35

Acarbose
(this agent is used in the management of diabetes to slow the digestion of carbohydrates and thus provide better postprandial control of blood glucose.)